Evolution has perfectioned proteins to perform various tasks vital for the upkeep of the biological world. Yet, them requiring specific environmental conditions to efficiently operate has hindered an otherwise vast opportunity of exploiting their unique functions for various industrial and bio-medical applications. Over recent decades, conjugating proteins with synthetic polymers has been explored as a promising strategy to push the functional capabilities of proteins beyond their natural limits. However, of the vast variety of components involved in constructing these chimeric molecules, the molecular level effects of initiators that are used to grow polymers from the protein surfaces are still not well understood and left unexploited. Therefore, in this talk, the effects caused by the ATRP initiator, N-2-bromo-2-methyl-propionyl-β-alanine N’-oxysuccinimide ester, on the structure-dynamics of a conjugated model protein, Rho130 will be presented. The formation of initiator clusters was revealed in areas of dense conjugation, using atomistic molecular dynamics simulations. These clusters were predicted to impose conformational stability to a previously identified highly dynamic unstructured C-terminal region of the protein, without altering the protein’s global structure-dynamic relationship. This novel in-silico observation could potentially expose avenues to obtain high-resolution structures of proteins containing highly dynamic regions, via X-ray crystallographic methods. Further, insights on, how the cluster forming interactions between initiators would be useful to predict the ability to produce homogenous protein-polymer bioconjugates, will be provided.

Unveiling the molecular-level effects of ATRP initiator clusters formation on unstructured regions of conjugated proteins

ACS Spring Meeting 2021

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